ResearchResearch Progress towards elimination of mother-to-child transmission of hepatitis B virus infection in China: a modelling analysis Zheng Hui,a Shevanthi Nayagam,b Polin Chan,c Wang Fuzhen,d Mark Thursz,e Yin Zundong,d Miao Ning,d Sun Xiaojin,d Fuqiang Cui,a Zhang Guomind & Timothy B Hallettb Objective To determine the projected burden of hepatitis B virus (HBV) in China, the intervention strategies that can eliminate mother- to-child transmission (MTCT) by 2030 or earlier and the measurable parameters that can be used to monitor progress towards this target. Methods We developed a dynamic, sex- and age-stratified model of the HBV epidemic in China, calibrated using hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) prevalence data from sequential national serosurveys (1979–2014) and the numbers of HBV-related cancer deaths (2012). We determined whether China can achieve elimination of MTCT of HBV by 2030 under current prevention interventions. We modelled various intervention scenarios to represent different coverage levels of birth-dose HBV vaccination, hepatitis B immunoglobulin to newborns of HBsAg-positive mothers and antiviral therapy (tenofovir) to HBeAg-positive pregnant women. Findings We project that, if current levels of prevention interventions are maintained, China will achieve the elimination target by 2029. By modelling various intervention scenarios, we found that this can be brought forward to 2025 by increasing coverage of birth-dose vaccination, or to 2024 by the administration of tenofovir to HBeAg-positive pregnant women. We found that achievement of the target by 2025 would be predicted by a measurement of less than 2% MTCT in 2020. Conclusion Our results highlight how high-quality national data can be combined with modelling in monitoring the elimination of MTCT of HBV. By demonstrating the impact of increased interventions on target achievement dates, we anticipate that other high-burden countries will be motivated to strengthen HBV prevention policies. Introduction HBV to their newborns.5,6 There is now accumulating evidence, particularly from China, that the additional use of tenofovir The global momentum towards the elimination of viral hepa- during the final trimester of pregnancy is a safe and effective titis is growing. The World Health Assembly adopted the first method of further reducing MTCT.7–10 However, the impact global viral hepatitis elimination target in 2016 in calling for a of this strategy at a population level is unknown. 90% reduction in new chronic hepatitis B virus (HBV) infec- In 2017, the National Health Commission of the People’s tions by 2030, and the Global health sector strategy outlined Republic of China (formerly the National Health and Fam- a target of achieving a childhood prevalence of hepatitis B ily Planning Commission of China) and the World Health surface antigen (HBsAg) of 0.1% by 2030.1 Organization (WHO) Western Pacific Region endorsed a In China, the government have identified HBV as a signifi- framework for the triple elimination of MTCT of human im- cant health issue, and the virus is one of six major infectious munodeficiency virus (HIV), HBV and syphilis by 2030.11 The diseases included in the latest 5-year Chinese national plan.2 focus has now shifted from HBV control to the elimination Substantial progress has been made over the past 20 years in of MTCT of HBV, the achievement of which by any country implementing high national levels of coverage of interventions has not yet been validated by WHO. Elimination of MTCT is to prevent both horizontal transmission (infant HBV vaccina- defined in China as an HBsAg prevalence of less than 0.1% tion) and vertical transmission (birth-dose HBV vaccination in children aged 1–4 years, a directly measurable indicator in within 24 hours of birth and hepatitis B immunoglobulin, national serosurveys. Ig). The results of sequential national serosurveys in China Given the global momentum and the available strategies reveal a reduction in the prevalence of HBsAg in children to further reduce MTCT of HBV, there exists the real possibil- younger than 5 years from 9.7% in 1992, to 1.0% in 2006 and ity of eliminating this route of transmission in China before to 0.3% in 2014.3 2030. Using a dynamic simulation model of the HBV epidemic Despite these public health efforts in China, there remains in China, we aim to determine: (i) the current and projected ongoing transmission of HBV. The major route is mother-to- burden of HBV nationwide; (ii) whether MTCT of HBV can child transmission (MTCT);4 even with the use of birth-dose be eliminated by 2030; (iii) which strategies could allow China HBV vaccination and hepatitis B Ig, about 2–9% of mothers to eliminate MTCT of HBV before 2030; and (iv) the indica- who test positive for hepatitis B e antigen (HBeAg) transmit tors that can be used to measure progress towards this target. a School of Public Health, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China. b Department of Infectious Disease Epidemiology, Imperial College London, London, England. c World Health Organization Regional Office for the Western Pacific, Manila, Philippines. d National Immunization Programme, Chinese Center for Disease Control and Prevention, Beijing, China. e Division of Digestive Diseases, Imperial College London, London, England. Correspondence to Fuqiang Cui (email: hepatitis2020@ 163 .com). (Submitted: 25 November 2019 – Revised version received: 10 September 2020 – Accepted: 14 September 2020 – Published online: 28 October 2020 ) 10 Bull World Health Organ 2021;99:10–18 | doi: http://dx.doi.org/10.2471/BLT.19.248146 Research Zheng Hui et al. Eliminating mother-to-child transmission of hepatitis B virus, China Table 1. Sources of transmission, calibration and intervention coverage data used to calibrate dynamic modelling of hepatitis B virus, China, 2019 Variable Value (%) Source MTCT parameters HBeAg− mother, birth-dose vaccination 0 Lu et al.12 HBeAg+ mother, birth-dose vaccination 0.127 Ying et al. (2017, personal communication) HBeAg− mother, birth-dose vaccination and hepatitis B Ig 0 Lu et al.12 HBeAg+ mother, birth-dose vaccination and hepatitis B Ig 0.056 Ying et al. (2017, personal communication) HBeAg+ mother, birth-dose HBV vaccination, hepatitis B Ig 0.01 Hyun et al.9 (to represent an 80% reduction in MTCT and tenofovir with addition of tenofovir) Calibration data Prevalence of HBsAg by sex and age, years Male, 1–4 9.71 China CDC National Serosurvey 197913 Male, 5–14 11.45–11.96 Male, 15–59 7.38–11.55 Male, 60–89 1.29–5.06 Female, 1–4 7.92 Female, 5–14 7.79–9.08 Female, 15–59 5.72–7.76 Female, 60–89 3.66–4.55 Male, 1–4 9.18 China CDC National Serosurvey 199214 Male, 5–14 10.89–11.94 Male, 15–59 8.07–12.28 Male, 60–64 11.76 Female, 1–4 7.30 Female, 5–14 7.88–9.07 Female, 15–59 5.87–8.97 Female, 60–64 14.81 Male, 1–4 1.21 China CDC National Serosurvey 200615 Male, 5–14 1.82–3.77 Male, 15–59 8.48–10.91 Female, 1–4 0. 93 Female, 5–14 1.37–2.95 Female, 15–59 5.79–7.47 Male, 1–4 0.35 China CDC National Serosurvey 201416 Male, 5–14 0.47–1.28 Male, 15–29 2.82–6.32 Female, 1–4 0.28 Female, 5–14 0.70–1.43 Female, 15–29 2.70–4.88 Prevalence of HBeAg by sex and age, years Male, 1–4 70.75 China CDC National Serosurvey 200617 Male, 5–14 66.38–70.54 Male, 15–59 10.60–52.67 Female, 1–4 66.20 Female, 5–14 64.71–68.35 Female, 15–59 11.86–56.79 Male, 1–4 87.46 China CDC National Serosurvey 20143 Male, 5–14 53.42–66.47 Male, 15–29 37.03–59.38 Female, 1–4 90.17 Female, 5–14 32.97–61.37 Female, 15–29 15.62–44.70 Intervention coverage Liu et al.,18 WHO19 Infant vaccination, 1992–2018 32.6–99.49 Birth-dose vaccination,1992–2018 23.5–96.05 −: negative; +: positive; CDC: Centers for Disease Control and Prevention; HBeAg: hepatitis B e antigen; HBsAg: hepatitis B surface antigen; HBV: hepatitis B virus; Ig: immunoglobulin; MTCT: mother-to-child transmission; WHO: World Health Organization. Bull World Health Organ 2021;99:10–18| doi: http://dx.doi.org/10.2471/BLT.19.248146 11 Research Eliminating mother-to-child transmission of hepatitis B virus, China Zheng Hui et al. Further analysis Table 2. Main intervention scenarios considered in achieving the elimination of mother-to-child transmission of hepatitis B virus, China, from 2019 Although elimination of MTCT of HBV is defined in China as a prevalence of HBsAg Intervention scenario % of relevant population covered of less than 0.1% in children aged 1–4 years, Birth-dose HBV Hepatitis B Ig Tenofovir there are alternative age ranges that can vaccination of all to newborns of to HBeAg+ be used. We therefore also modelled the newborns HBsAg+ mothers pregnant women outcome of status quo interventions when changing the age group in which preva- Status quo (2016) 95.9 99.5 0.0 lence is measured to all children younger A: Increased birth-dose 99.0 99.5 0.0 than 5 years and to children exactly 5 years. vaccination from 2019 We also performed a sensitivity B: Scenario A with increased 99.0 99.9 0.0 analysis to explore how five different hepatitis B Ig from 2019 fertility projections would affect out- C: Scenario B with tenofovir 99.0 99.9 50.0 comes.